Introduction: Peroxisome proliferatior-activated receptor-γ2 (PPAR-γ2) plays a crucial role in adipogenesis and has been shown to be involved in the control of immunoregulation and inflammation. Orbital fibroblast differentiation to adipocytes is a PPAR-γ dependent process essential for pathogenic tissue remodeling in Graves orbitopathy (GO). Genetic variation in PPAR-γ2 gene may modulate expression and/or function of molecule encoded by this gene.
Purpose: The occurrence and associations of the PPAR-γ2 Pro12Ala mutation with clinical manifestation of GO were studied.
Material and methods: The Pro12Ala polymorphism was determined in total 742 Lower Silesia Caucasians including 276 Graves disease (GD) patients (212 GO patients and 64 subjects without eye changes) and 466 healthy controls using PCR-RFLP technique (with the use of restriction enzyme HpaII).
Results: The distribution of The Pro12Ala polymorphism did not differ between GD patients and healthy subjects. Within the GD group the Ala allele and a presence of Ala variant (Pro12Ala or Ala12Ala genotype) decreased the risk of GO (OR=0.33, P=1.2e5, 95%CI:0.190.55 and OR=0.32, P=0.00013, 95%CI:0.170.58, respectively). Moreover, Ala12Ala genotype was observed only in patients without GO (5.2%, P=0.007, after Yates correction). However the distribution of genotypes and alleles in studied marker was similar in patients shared-out according to severity as well as activity status of GO. The female carriers of Ala12 allele statistically seldom develop GO (P=0.0005, OR=0.31, 95%CI:0.160.61). Additionally, the presence of Ala12 allele increased the risk of active GO in men (P=0.04 after Yates correction, OR=6.47, 95% CI: 1.2533.52).
Conclusions: For the first time we pointed that the presence of Ala variant (Ala12Ala and/or Pro12Ala genotype) in unique exon B in PPAR-γ2 gene strongly reduces the risk of GO and the Al12Ala genotype was seen only in patients without GO so may be considered as a protective factor.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector